Drugs to Avoid in Patients on Tyrosine Kinase Inhibitors

Editor’s note: More and more people with cancer are being treated with drugs known as tyrosine kinase inhibitors (TKIs). As with any other drug, oncologists who prescribe TKIs must be aware of other drugs a patient is taking to ensure there will not be a dangerous drug-drug interaction. Researchers recently published a report outlining known and potential drug-drug interactions between TKIs and other drugs. Oncologists and patients may wish to take these into account when considering cancer treatment with TKIs.

“With the rapid and widespread uptake of tyrosine kinase inhibitors (TKIs) in oncology over the past several years, serious drug–drug interactions are an “increasing risk,” according a new report.

“To guarantee the safe use of TKIs, ‘a drugs review for each patient is needed,’ write Frank G.A. Jansman, PharmD, PhD, from Deventer Hospital in the Netherlands, and colleagues in a review published in the July issue of the Lancet Oncology.

“The review provides a comprehensive overview of known and suspected interactions between TKIs and conventional prescribed drugs, over-the-counter drugs, and herbal medicines.

“All 15 TKIs approved to date by the US Food and Drug Administration or the European Medicines Agency are evaluated.

“They are axitinib (Inlyta, Pfizer), crizotinib (Xalkori, Pfizer), dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), erlotinib (Tarceva, Osi Pharmaceuticals), gefitinib (Iressa, AstraZeneca), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), nilotinib (Tasigna, Novartis), pazopanib (Votrient, GlaxoSmithKline), regorafenib (Stivarga, Bayer), ruxolitinib (Jakafi, Incyte), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), vandetanib (Caprelsa, AstraZeneca), and vemurafenib (Zelboraf, Roche).”


At ASCO, Next-Gen EGFR Inhibitors Show Early Promise in Lung Cancer Patients with T790M Mutations

“Next-generation EGFR inhibitors for treating metastatic non-small cell lung cancer patients who have acquired resistance to first-generation drugs in this class accurately hit mutant EGFR tumor cells and caused fewer serious side effects, early data presented at a major cancer conference showed.

“Researchers at the American Society of Clinical Oncology’s annual meeting here this week, presented preliminary data from human studies on three next-generation EGFR inhibitors: AstraZeneca’s AZD9291, Clovis Oncology’s CO-1686, and Hanmi Pharmaceutical’s HM61713. All three agents showed promising activity against patients who had EGFR mutations, had received prior treatment with a first-generation tyrosine kinase inhibitor – such as Roche’s Tarceva (erlotinib) and AstraZeneca’s Iressa (gefinitib) – and had T790M mutations.”

Editor’s note: For a more reader-friendly explanation of these new drugs, check out the “Drug resistance” section of our Chief Scientist’s latest blog post.


Thwarting Drug Resistance in Lung Cancer


If you’ve read up on lung cancer research in the last few years, you probably know that large strides have been made in targeted therapies for non-small cell lung cancer (NSCLC). Targeted therapies are drugs that identify and attack specific mutated proteins that are detected in tumors. Because noncancerous cells do not have these specific mutations, targeted therapies can make a beeline for cancer, while leaving healthy tissue unharmed. Continue reading…


Erlotinib and Gefitinib Offer Similar Benefit in EGFR-Mutated Non–Small Cell Lung Cancer

“A retrospective study has shown that two targeted therapy drugs—erlotinib (Tarceva) and gefitinib (Iressa)—achieved similar outcomes among people with metastatic or recurrent non–small cell lung cancer (NSCLC) harboring an EGFR mutation. These EGFR tyrosine kinase inhibitors have previously been reported to offer benefit over standard chemotherapy as first-line treatment of EGFR-positive advanced NSCLC. The study findings by Lim et al are published in the Journal of Thoracic Oncology.

“Erlotinib is used worldwide, and gefitinib is widely used in Asian countries and recently in Europe (only for patients with tumors harboring EGFR mutations) but not in the United States. Indirect comparisons of the two agents have resulted in inconsistency with regard to progression-free survival, and until now, the agents have not been compared head-to-head in patients with EGFR-positive NSCLC.”

Editor’s note: Erlotinib and gefitinib are targeted therapies. Learn more.


Gefitinib, Erlotinib Increased Risk for Interstitial Lung Disease in Patients with Advanced NSCLC

“Patients treated with advanced non–small cell lung cancer treated with gefitinib and erlotinib demonstrated a significant increased risk for all-grade and fatal interstitial lung disease events, according to results of a systematic review and meta-analysis.

“Erlotinib (Tarceva, Genentech) and gefitinib (Iressa, AstraZeneca), both of which are oral epidermal growth factor receptor tyrosine kinase inhibitors, are commonly used during treatment of advanced NSCLC. However, the overall risk for interstitial lung disease events are not known.”


Lung Cancer Drug Disappoints in 2 Late-Stage Trials

In a recent phase III clinical trial, the cancer drug dacomitinib was no more effective than a placebo at prolonging survival for patients with advanced non-small cell lung cancer (NSCLC) for whom standard therapy had failed. Like the targeted drugs erlotinib (Tarceva) and gefitinib (Iressa), dacomitinib blocks the protein EGFR, but it also inhibits a number of similar, related proteins. Another trial compared dacomitinib to Tarceva in NSCLC patients who had previously received at least one EGFR inhibitor. Dacomitinib did not increase time without cancer worsening compared to Tarceva. Results from a third phase III trial, which compares dacomitinib to Iressa in NSCLC patients with EGFR mutations, are expected next year.


Molecular Marker Predicts Response to Iressa and Tarceva

A molecule named Mig 6 may help predict how much a patient will benefit from EGFR inhibitors like Tarceva (erlotinib) or Iressa (gefitinib). Preliminary results from an ongoing study reveal that cancer cells that are resistant to EGFR inhibitors have high Mig 6 levels. In an animal model of non-small cell lung cancer (NSCLC) without EGFR mutations, higher Mig 6 levels predicted more resistance to EGFR inhibitor treatment. Finally, NSCLC patients with low Mig 6 levels were more likely to survive for over a year after EGFR inhibitor treatments. Mig 6 may help identify patients who would most benefit from EGFR inhibitors.


Trial Investigating Iressa After Lung Cancer Surgery Terminated Early

A clinical trial investigating whether the cancer drug gefinitib (Iressa) can improve outcomes after lung cancer surgery has been ended early. The trial followed patients who were given either Iressa or a placebo after receiving surgery to completely remove their non-small cell lung cancer (NSCLC). When two other studies showed no benefit of Iressa in similar disease situations, the trial was terminated. Due to the early termination of the trial, no firm conclusions can be drawn from the results. However, analysis of the already collected data suggests that Iressa likely did not improve survival, or delay cancer recurrence in this patient population, and may have indeed been harmful.


Cancer Researcher: No Need for Further EGFR Inhibitor Versus Chemotherapy Trials

No more trials comparing EGFR inhibitors to chemotherapy in patients with non-small cell lung cancer (NSCLC) should be conducted, argues an editorial by cancer researcher Corey Langer. Eight separate trials have found that EGFR inhibitors like erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif) produce better results than chemotherapy in NSCLC patients who have mutations in the EGFR gene. No further confirmation is needed, Langer contends. Instead, research should focus on ways to overcome the drug resistance that many patients eventually develop to EGFR inhibitors, meaningfully extending overall survival in NSCLC, and directly comparing the relative effectiveness and safety of Tarceva, Iressa, and Gilotrif.